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60.1: Pilomatricoma and Pilomatrix Carcinoma

Edward F. Chan; Uri Gat; Ramanuj Dasgupta; Elaine Fuchs

Abstract

Abstract

Pilomatricoma is a benign hair follicle tumor that is thought to be the most common solid cutaneous tumor in patients 20 years of age or younger. It demonstrates differentiation toward the compartment of cells in the matrix of the hair bulb that forms the hair shaft. These tumors typically present as solitary, firm nodules on the head, neck, and upper extremities. Multiple pilomatricomas are found in 4 percent of cases. There is a bimodal age of presentation, with most cases occurring in the first and sixth decades. In patients younger than 20 years of age, there is a male:female ratio of 1:2.5.

Pilomatrix carcinoma is relatively rare; there have been approximately 70 reports in the literature. Unlike pilomatricomas, pilomatrix carcinomas have a male:female ratio of 2:1 and occur at a later age, with a mean age of 48. This tumor may have an invasive growth pattern, with spread into the underlying bone. Local recurrence occurs in 60 percent of cases and metastatic disease occurs in 10 percent of cases.

The histologic appearance of a pilomatricoma is of a well-circumscribed tumor in the lower dermis to subcutis comprised of coalescing, irregularly shaped islands of epithelial cells. Two basic cell types form these epithelial islands: basophilic cells and eosinophilic shadow cells. The basophilic cells tend to be at the periphery or sides of the tumor islands and possess scant cytoplasm, indistinct cell borders, basophilic and hyperchromatic nuclei, and numerous mitoses. The eosinophilic shadow cells are at the center of the tumor and show distinct cell borders, faintly eosinophilic cytoplasm, and a central oval clear area which is a shadow of the lost nucleus. These shadow cells form from the basophilic cells and there may be a transition zone where the basophilic cells become more eosinophilic with development of pyknotic nuclei. There are often foci of calcification and ossification associated with the shadow cells.

In pilomatrix carcinoma, there are large, anaplastic, hyperchromatic basophilic cells with numerous mitoses, some of which may be atypical. The basophilic cells show variation in nuclear size, with coarse chromatin, and prominent nucleoli. There are cystic areas with central necrosis and shadow cells. Vascular and perineural invasion may also be present.

Some syndromes involve pilomatricomas as one of several complex traits. These disorders include myotonic dystrophy, Gardner syndrome, and the Rubinstein-Taybi syndrome. In addition, there are reported cases of familial pilomatricomas without other systemic manifestations. In contrast to the sporadic cases of pilomatricoma in which a solitary lesion is typical, in the case of familial pilomatricomas, the tumors are often multiple.

A high percentage of pilomatricomas possess β-catenin missense mutations clustered in the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. The initial work that led to this finding developed from the observation that similar tumors develop in transgenic mice expressing a keratin promoter-driven, stable form of β-catenin truncated at its amino terminus. In addition, nuclear LEF-1 is present in the basophilic cells of the tumor, thus providing further biochemical evidence that pilomatricomas are derived from hair matrix cells. These findings point to β-catenin/LEF misregulation as a major cause of tumorigenesis in pilomatricomas.